Regioselective anti-Silyllithiation of Propargylic Amines

Abstract

The regioselective anti-silyllithiation of propargylic amines is developed to facilitate the efficient synthesis of alkenylsilanes. This reaction generates an alkenyllithium intermediate that is stabilized by the formation of a five-membered cyclic structure through intramolecular coordination of the nitrogen functional group. Upon subsequent treatment with an electrophile, the alkenyllithium intermediate is further functionalized to afford tetrasubstituted allylic amines bearing a β-silicon substituent.

Key words

silyllithium - alkenylsilane - allylamine - one-pot synthesis - remote stereocontrol

Publication History

Received: 06 February 2023

Accepted after revision: 06 March 2023

Accepted Manuscript online:
06 March 2023

Article published online:
12 April 2023

• References and Notes

• 1 Organosilicon Chemistry: Novel Approaches and Reactions . Hiyama T, Oestreich M. Wiley-VCH; Weinheim: 2020
• 2 Beletskaya I, Moberg C. Chem. Rev. 2006; 106: 2320
• 3 Suginome M, Ito Y. Chem. Rev. 2000; 100: 3221
• 4 Trost BM, Ball ZT. Synthesis 2005; 853
• 5 Lim DS. W, Anderson EA. Synthesis 2012; 44: 983
• 6 Wilkinson JR, Nuyen CE, Carpenter TS, Harruff SR, Van Hoveln R. ACS Catal. 2019; 9: 8961
• 7 Hayami H, Sato M, Kanemoto S, Morizawa Y, Oshima K, Nozaki H. J. Am. Chem. Soc. 1983; 105: 4491
• 8 Tang J, Okada K, Shinokubo H, Oshima K. Tetrahedron 1997; 53: 5061
• 9 Trost BM, Ball ZT, Jöge T. Angew. Chem. Int. Ed. 2003; 42: 3415
• 10 Trost BM, Ball ZT. J. Am. Chem. Soc. 2005; 127: 17644
• 11 Rummelt SM, Radkowski K, Roşca D.-A, Fürstner A. J. Am. Chem. Soc. 2015; 137: 5506
• 12 Roşca D.-A, Radkowski K, Wolf LM, Wagh M, Goddard R, Thiel W, Fürstner A. J. Am. Chem. Soc. 2017; 139: 2443
• 13 Karad SN, Saito H, Shimokawa J, Yorimitsu H. J. Org. Chem. 2022; in press DOI: 10.1021/acs.joc.2c01795.
• 14 Richey HG. Jr, Moses LM, Domalski MS, Erickson WF, Heyn AS. J. Org. Chem. 1981; 46: 3773
• 15 Richey HG. Jr, Heyn AS, Erickson WF. J. Org. Chem. 1983; 48: 3821
• 16 Regioselective anti-Silyllithiation of Propargylic Amines 1; General Procedure The synthesis of 3aa is representative. A 20-mL Schlenk tube was charged with tert-butyl (3-phenylprop-2-yn-1-yl)carbamate (1a) (115.5 mg, 0.499 mmol) and toluene (5.0 mL) under a nitrogen atmosphere, and the resulting solution was cooled to –40 °C. To the mixture was added PhMe₂SiLi (2a) (1.5 M in THF, 1.2 mL, 1.75 mmol, 3.5 equiv) dropwise. After stirring the mixture for 3 h at –40 °C, saturated aqueous NH₄Cl (1.0 mL) was added at 0 °C. The resulting biphasic solution was extracted with EtOAc (3 × 10 mL). The combined organic layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane/CH₂Cl₂ = 1:2) to provide 3aa (148.6 mg, 0.404 mmol, 81%) as a pale yellow solid. ¹H NMR (600 MHz, CDCl₃): δ = 7.53–7.50 (m, 2 H), 7.40 (br s, 1 H), 7.38–7.34 (m, 3 H), 7.24–7.20 (m, 3 H), 7.15–7.12 (m, 2 H), 4.66 (br s, 1 H), 3.99 (d, J = 6.1 Hz, 2 H), 1.49 (s, 9 H), 0.20 (s, 6 H). ¹³C NMR (151 MHz, CDCl₃): δ = 155.6, 143.6, 139.4, 139.1, 138.6, 133.8, 129.0, 128.6, 127.9, 127.8, 127.2, 79.3, 47.7, 28.5, –1.5. HRMS (APCI-MS, positive): m/z [M – tBu]⁺ calcd for ­C₁₈H₂₀NO₂Si: 310.1258; found: 310.1269.
• 17 Robak MT, Herbage MA, Ellman JA. Chem. Rev. 2010; 110: 3600
• 18 Patterson AW, Ellman JA. J. Org. Chem. 2006; 71: 7110
• 19 CCDC 1982977 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 20 Feng Q, Wu H, Li X, Song L, Chung LW, Wu Y.-D, Sun J. J. Am. Chem. Soc. 2020; 142: 13867
• 21 Urbanaitė A, Jonušis M, Bukšnaitienė R, Balkaitis S, Čikotienė I. Eur. J. Org. Chem. 2015; 7091